Permeabilizing Cell Membranes with Electric Fields
The biological impact of exogenous, alternating electric fields (AEFs) and direct-current electric fields has a long history of study, ranging from effects on embryonic development to influences on wound healing. In this article, we focus on the application of electric fields for the treatment of ca...
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MDPI AG
2021-05-01
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Series: | Cancers |
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Online Access: | https://www.mdpi.com/2072-6694/13/9/2283 |
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author | Alondra A. Aguilar Michelle C. Ho Edwin Chang Kristen W. Carlson Arutselvan Natarajan Tal Marciano Ze’ev Bomzon Chirag B. Patel |
author_facet | Alondra A. Aguilar Michelle C. Ho Edwin Chang Kristen W. Carlson Arutselvan Natarajan Tal Marciano Ze’ev Bomzon Chirag B. Patel |
author_sort | Alondra A. Aguilar |
collection | DOAJ |
description | The biological impact of exogenous, alternating electric fields (AEFs) and direct-current electric fields has a long history of study, ranging from effects on embryonic development to influences on wound healing. In this article, we focus on the application of electric fields for the treatment of cancers. In particular, we outline the clinical impact of tumor treating fields (TTFields), a form of AEFs, on the treatment of cancers such as glioblastoma and mesothelioma. We provide an overview of the standard mechanism of action of TTFields, namely, the capability for AEFs (e.g., TTFields) to disrupt the formation and segregation of the mitotic spindle in actively dividing cells. Though this standard mechanism explains a large part of TTFields’ action, it is by no means complete. The standard theory does not account for exogenously applied AEFs’ influence directly upon DNA nor upon their capacity to alter the functionality and permeability of cancer cell membranes. This review summarizes the current literature to provide a more comprehensive understanding of AEFs’ actions on cell membranes. It gives an overview of three mechanistic models that may explain the more recent observations into AEFs’ effects: the voltage-gated ion channel, bioelectrorheological, and electroporation models. Inconsistencies were noted in both effective frequency range and field strength between TTFields versus all three proposed models. We addressed these discrepancies through theoretical investigations into the inhomogeneities of electric fields on cellular membranes as a function of disease state, external microenvironment, and tissue or cellular organization. Lastly, future experimental strategies to validate these findings are outlined. Clinical benefits are inevitably forthcoming. |
first_indexed | 2024-03-10T11:34:08Z |
format | Article |
id | doaj.art-e0f3459516c140509d756bd2acd70eea |
institution | Directory Open Access Journal |
issn | 2072-6694 |
language | English |
last_indexed | 2024-03-10T11:34:08Z |
publishDate | 2021-05-01 |
publisher | MDPI AG |
record_format | Article |
series | Cancers |
spelling | doaj.art-e0f3459516c140509d756bd2acd70eea2023-11-21T19:02:26ZengMDPI AGCancers2072-66942021-05-01139228310.3390/cancers13092283Permeabilizing Cell Membranes with Electric FieldsAlondra A. Aguilar0Michelle C. Ho1Edwin Chang2Kristen W. Carlson3Arutselvan Natarajan4Tal Marciano5Ze’ev Bomzon6Chirag B. Patel7Molecular Imaging Program at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USAMolecular Imaging Program at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USAMolecular Imaging Program at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USABeth Israel Deaconess Medical Center, Department of Neurosurgery, Harvard Medical School, Boston, MA 02215, USAMolecular Imaging Program at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USANovocure, Ltd., 31905 Haifa, IsraelNovocure, Ltd., 31905 Haifa, IsraelMolecular Imaging Program at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USAThe biological impact of exogenous, alternating electric fields (AEFs) and direct-current electric fields has a long history of study, ranging from effects on embryonic development to influences on wound healing. In this article, we focus on the application of electric fields for the treatment of cancers. In particular, we outline the clinical impact of tumor treating fields (TTFields), a form of AEFs, on the treatment of cancers such as glioblastoma and mesothelioma. We provide an overview of the standard mechanism of action of TTFields, namely, the capability for AEFs (e.g., TTFields) to disrupt the formation and segregation of the mitotic spindle in actively dividing cells. Though this standard mechanism explains a large part of TTFields’ action, it is by no means complete. The standard theory does not account for exogenously applied AEFs’ influence directly upon DNA nor upon their capacity to alter the functionality and permeability of cancer cell membranes. This review summarizes the current literature to provide a more comprehensive understanding of AEFs’ actions on cell membranes. It gives an overview of three mechanistic models that may explain the more recent observations into AEFs’ effects: the voltage-gated ion channel, bioelectrorheological, and electroporation models. Inconsistencies were noted in both effective frequency range and field strength between TTFields versus all three proposed models. We addressed these discrepancies through theoretical investigations into the inhomogeneities of electric fields on cellular membranes as a function of disease state, external microenvironment, and tissue or cellular organization. Lastly, future experimental strategies to validate these findings are outlined. Clinical benefits are inevitably forthcoming.https://www.mdpi.com/2072-6694/13/9/2283alternating electric fields (AEFs), bioelectrorheologycancercell membranecell modelingelectroporationglioblastoma |
spellingShingle | Alondra A. Aguilar Michelle C. Ho Edwin Chang Kristen W. Carlson Arutselvan Natarajan Tal Marciano Ze’ev Bomzon Chirag B. Patel Permeabilizing Cell Membranes with Electric Fields Cancers alternating electric fields (AEFs), bioelectrorheology cancer cell membrane cell modeling electroporation glioblastoma |
title | Permeabilizing Cell Membranes with Electric Fields |
title_full | Permeabilizing Cell Membranes with Electric Fields |
title_fullStr | Permeabilizing Cell Membranes with Electric Fields |
title_full_unstemmed | Permeabilizing Cell Membranes with Electric Fields |
title_short | Permeabilizing Cell Membranes with Electric Fields |
title_sort | permeabilizing cell membranes with electric fields |
topic | alternating electric fields (AEFs), bioelectrorheology cancer cell membrane cell modeling electroporation glioblastoma |
url | https://www.mdpi.com/2072-6694/13/9/2283 |
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